Ketotifen (Zaditen®, Zaditor®, Sandoz, Novartis) is a Generation-1 antihistamine that is mainly used for the treatment of allergic rhinitis. Ketotifen may be the most sedating of all marketed antihistamines and the unusually severe sedative side effects of ketotifen have limited the therapeutic usefulness of the drug. In the USA, ketotifen is only used as eye drops (Zaditor®, Novartis) to alleviate the symptoms of allergic conjunctivitis in humans and does not cause sedation due to the extremely low systemic concentrations of the drug after local administration to the eyes.
Norketotifen, an active metabolite of ketotifen, is an achiral molecule, but has two atropisomers, S-norketotifen and R-norketotifen, as has previously been described in U.S. Pat. Nos. 7,226,934 and 7,557,128. As explained in U.S. Pat. Nos. 7,226,934 and 7,557,128, norketotifen also has a significant sedation effect when studied in the art-accepted mouse model of sedation, and further, the sedative effects were attributed to the R-isomer. It was thus proposed that only the S-isomer could be administered without significant sedation effects.
Approximately 1500 fungi have been described, and some of them exist normally on the skin of various mammal species, including dogs, cats and humans. Malassezia species form a family of 6 to 10 lipolytic fungi. Overgrowth of Malassezia species causes toxic or immunological reactions and contributes to various dermal diseases and conditions, such as for example, adult seborrheic dermatitis, atopic dermatitis, dandruff, Malassezia dermatitis, Malassezia folliculitis, pityriasis versicolor, psoriasis, rosacea, seborrheic dermatitis and tinea. These disorders are typically treated with medication for the underlying condition in combination with an antifungal medication that can be administered orally or topically to the skin.
What is needed are methods of treating inflammatory and infectious dermal disorders without causing sedation or the much feared side effects of current medications for such diseases in dogs, which consist of corticosteroids and immunosuppressant drugs. Also needed are improved topical treatments for dermal disorders.